Messerschmidt Daniel, de Vries Wilhelmine N, Lorthongpanich Chanchao, Balu Sathish, Solter Davor, Knowles Barbara B
Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Immunos 06-06, 138648, Singapore Institute of Molecular and Cellular Biology, A*STAR, Proteos 5-02, 138673, Singapore.
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
Development. 2016 Jun 1;143(11):1993-9. doi: 10.1242/dev.133439.
β-catenin (CTNNB1) is integral to cell adhesion and to the canonical Wnt signaling pathway. The effects of maternal and zygotic CTNNB1 on embryogenesis have each been separately assessed, whereas the effect of its total absence has not. As the 'traditional' conditional Ctnnb1 knockout alleles give rise to truncated CTNNB1 fragments, we designed a new knockout allele incapable of CTNNB1 production. Mouse embryos lacking intact maternal/zygotic CTNNB1 from two knockout strains were examined in detail. Preimplantation embryos are formed, yet abnormalities in their size and shape were found throughout pre- and early postimplantation development. In the absence of the zona pellucida, embryos lacking CTNNB1 undergo fission and these separated blastomeres can become small trophoblastic vesicles, which in turn induce decidual reactions. Comparing the severity of this defective adhesion phenotype in embryos bearing the null allele with those carrying the 'traditional' knockout allele suggests a hypomorphic effect of the truncated CTNNB1 protein fragment, an important observation with possible impact on previous and future studies.
β-连环蛋白（CTNNB1）对于细胞黏附以及经典Wnt信号通路至关重要。母源和合子源CTNNB1对胚胎发育的影响已分别进行评估，但其完全缺失的影响尚未评估。由于“传统”的条件性Ctnnb1敲除等位基因会产生截短的CTNNB1片段，我们设计了一种无法产生CTNNB1的新敲除等位基因。对来自两个敲除品系的缺乏完整母源/合子源CTNNB1的小鼠胚胎进行了详细检查。植入前胚胎能够形成，但在植入前和植入后早期发育过程中均发现其大小和形状存在异常。在没有透明带的情况下，缺乏CTNNB1的胚胎会发生分裂，这些分离的卵裂球可形成小的滋养层小泡，进而诱导蜕膜反应。将携带无效等位基因的胚胎与携带“传统”敲除等位基因的胚胎中这种黏附缺陷表型的严重程度进行比较，提示截短的CTNNB1蛋白片段具有亚效性作用，这一重要观察结果可能会对既往及未来研究产生影响。
